Potassium Carbonate → 2-[2-(6-Fluoro-pyridin-2-yl)-imidazol-1-ylmethyl]-3-methoxy-5-phenyl-pyrazine

HRID 1609836Notes

Reaction equation

Cl[CH2:2][C:3]1[C:8]([O:9][CH3:10])=[N:7][C:6]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:5][N:4]=1.[F:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]2[NH:25][CH:26]=[CH:27][N:28]=2)[N:19]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:17][C:18]1[N:19]=[C:20]([C:24]2[N:28]([CH2:2][C:3]3[C:8]([O:9][CH3:10])=[N:7][C:6]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)=[CH:5][N:4]=3)[CH:27]=[CH:26][N:25]=2)[CH:21]=[CH:22][CH:23]=1

Participants

Conditions

Temperature: 45 °C

Procedure

A mixture of 2-chloromethyl-3-methoxy-5-phenyl-pyrazine (70 mg, 0.30 mmol), 2-fluoro-6-(1H-imidazol-2-yl)-pyridine (48 mg, 0.294 mmol) and K2CO3 (123 mg, 0.9 mmol) in DMF (5 mL) is stirred at 45° C. for 16 hours. On cooling, the reaction is quenched with saturated NH4Cl (2 mL) and extracted with DCM (3×10 mL). The combined organic layers are dried and solvent removed. PTLC separation (10% MeOH in DCM) gives 91 mg of 2-[2-(6-fluoro-pyridin-2-yl)-imidazol-1-ylmethyl]-3-methoxy-5-phenyl-pyrazine as an oil. 1H NMR (CDCl3) 8.41 (s, 1H), 8.08 (dd, 1H), 7.95–7.99 (m, 2H), 7.80 (dd, 1H), 7.42–7.49 (m, 3H), 7.22 (s, 1H), 7.15 (s, 1H), 6.77 (dd, 1H), 5.98 (s, 2H), 4.08 (s, 3H). B. 3-Methoxy-5-phenyl-2-(2-thiazol-2-yl-imidazol-1-ylmethyl)-pyrazine (Compound 2) 1. Synthesis of 2-(1H-imidazol-2-yl)-thiazole

Workup

temperatureOn cooling
customthe reaction is quenched with saturated NH4Cl (2 mL)
extractionextracted with DCM (3×10 mL)
customThe combined organic layers are dried
customsolvent removed
customPTLC separation (10% MeOH in DCM)

Sources & evidence

ORD record: ord-3cbdb311c5ee49c88288efb153017b1c
Source dataset: uspto-grants-2006_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06982268B2

Reaction notes

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